A Randomized Phase IIa Efficacy and Safety Study of Radium-223 Dichloride With Abiraterone Acetate or Enzalutamide in Metastatic Castration-resistant Prostate Cancer (CRPC)

Brief Summary

The primary objective in this study is to evaluate bone scan response at Week 24 based on the quantified technetium-99 bone scan lesion area (BSLA). The safety of radium-223 dichloride in combination with abiraterone acetate or enzalutamide will be investigated. The study will evaluate radiological progression free survival, overall survival, and skeletal events. This study will also explore the clinical utility of different imaging modalities (whole body quantified technetium-99 bone scan, DW-MRI \[diffusion-weighted magnetic resonance imaging\] and NaF \[sodium fluoride\] PET-CT \[positron emission tomography-computed tomography\] scan) and will have a separate central radiological review for applicable secondary and exploratory imaging endpoints. All subjects will be randomized as assigned randomly by the IXRS (interactive voice / web response system) system in a 1:1:1 ratio into one of the treatment arms: radium-223 dichloride alone, 50 kBq/kg (55 kBq/kg after implementation of NIST \[National Institute of Standards and Technology\] update) every 4 weeks for up to 6 doses; radium-223 dichloride, 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks up to 6 doses together with abiraterone acetate 1,000 mg daily and prednisone 5 mg bid (twice daily); radium-223 dichloride 50 kBq/kg (55 kBq/kg after implementation of NIST update) every 4 weeks up to 6 doses together with enzalutamide 160 mg daily. The study will consist of screening, treatment and follow-up periods. Study will continue until disease progression as determined by investigator, or when patient meets criteria for withdrawal from study. Subjects in treatment arms with abiraterone/prednisone or enzalutamide will have the option to continue taking oral study therapy until the end of the study (2 years from the last dose of radium-223 dichloride) if the investigator deems the subject may benefit and there is no clinical or radiological progression. Subjects who discontinue all study treatment prior to 2 years from last radium-223 dichloride treatment will enter active follow-up. During the active follow-up period, the subject will have a safety visit at the clinic every 12 weeks from the EOT (end of treatment) for up to 2 years from the last dose of radium-223 dichloride. Beyond 2 years from last radium-223 dichloride treatment,subjects will enter long-term follow-up and will be followed via phone contact at intervals to assess for safety (hematological toxicity and new primary malignancies) and overall survival. A separate long-term safety follow-up study protocol is planned. Once implemented, the study subjects surviving after the end of the active follow-up will be transitioned to this separate long-term safety follow-up protocol.

Brief Title

Categories

Prostate Cancer

Cancer

Endocrine System Cancers

Gastrointestinal (GI) Cancers

Gynecologic Cancers

Lung & Chest Cancers

Blood & Bone Marrow Cancers

Completion Date

2018-06-26

Completion Date Type

Actual

Conditions

Prostatic Neoplasms

Eligibility Criteria

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate
* Known castration-resistant disease
* Serum PSA ≥2 ng/mL (μg/L)
* Multiple skeletal metastases (≥2 hot spots) on bone scan
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.
* Life expectancy ≥6 months
* Adequate hematologic, hepatic, and renal function

Exclusion Criteria:

* History of visceral metastasis, or visceral metastases
* Malignant lymphadenopathy with lymph nodes exceeding 3 cm in short axis diameter
* Medical condition that would make prednisone (corticosteroid) use contraindicated
* Any chronic medical condition requiring a higher dose of corticosteroid than 5 mg prednisone bid
* Treatment with more than one chemotherapy agent for prostate cancer
* Prior systemic radiotherapy and hemibody external radiotherapy
* History of pituitary or adrenal dysfunction
* Chronic conditions associated with non-malignant abnormal bone growth (e.g., confirmed Paget's disease of bone)
* Atrial fibrillation, or other cardiac arrhythmia requiring medical therapy
* History of seizures (taking/not taking anticonvulsants), arteriovenous malformation in the brain, head trauma with loss of consciousness
* Central nervous system (CNS) metastases

Inclusion Criteria

Inclusion Criteria:

* Histologically or cytologically confirmed adenocarcinoma of the prostate
* Known castration-resistant disease
* Serum PSA ≥2 ng/mL (μg/L)
* Multiple skeletal metastases (≥2 hot spots) on bone scan
* Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0 to 2.
* Life expectancy ≥6 months
* Adequate hematologic, hepatic, and renal function

Gender

Male

Gender Based

false

Healthy Volunteers

No

Last Update Post Date

Tue, 07/23/2019 - 12:00

Last Update Post Date Type

Actual

Last Update Submit Date

Thu, 07/04/2019 - 12:00

Minimum Age

18 Years

NCT Id

NCT02034552

Org Class

Industry

Org Full Name

Bayer

Org Study Id

16544

Overall Status

Completed

Phases

Phase 2

Primary Completion Date

Fri, 07/15/2016 - 12:00

Primary Completion Date Type

Actual

Official Title

A Randomized Open-label Phase IIa Study Evaluating Quantified Bone Scan Response Following Treatment With Radium-223 Dichloride Alone or in Combination With Abiraterone Acetate or Enzalutamide in Subjects With Castration-resistant Prostate Cancer Who Have Bone Metastases

Primary Outcomes

Outcome Description

Radiological bone scan response based on change from baseline of digitized technetium-99 bone scans using computer-aided detection software. Responder (R): 30% or greater resolution of the BSLA compared to baseline. Stable Disease (SD): Not meeting the criteria for R, PD, or UE. Progressive Disease (PD): Two or more new areas of radiotracer uptake attributable to metastatic disease in regions of bone that had not previously shown radiotracer uptake or greater than 30% increase from baseline in BSLA attributable to metastatic disease. Unable to Evaluate (UE): Assigned if bone scan results cannot be interpreted due to inconsistent image acquisition parameters compared to the reference scan, incomplete imaging, or other similar technical deficiencies.

Outcome Measure

Patient Bone Scan Response Rate

Outcome Time Frame

At 24 weeks

Outcome Description

Bone scan lesion area was defined as the sum of the pixel areas (cm2) of the set of the whole body technetium-99 bone scan imaging pixels identified as bone lesion.

Outcome Measure

Bone Scan Lesion Area

Outcome Time Frame

At 24 weeks

Secondary Outcomes

Outcome Time Frame

From randomization to radiological disease progression or death from any cause (about 30.82 months )

Outcome Measure

Radiological Progression Free Survival

Outcome Time Frame

From the randomization date to the date of radiological disease progression (about 30.82months)

Outcome Measure

Time to Radiological Progression

Outcome Time Frame

From the randomization date to the date of radiological bone progression (about 30.82 months)

Outcome Measure

Time to Radiological Bone Progression

Outcome Time Frame

From the randomization date to the first SSE on or following the randomization date (about 30.82 months)

Outcome Measure

Time to First Symptomatic Skeletal Event

Outcome Time Frame

From the randomization date to the first SSE on or following the randomization date or death, whichever occurred first (about 32.39 months)

Outcome Measure

Symptomatic Skeletal Event-free Survival

Outcome Time Frame

From the randomization date to the date of death due to any cause (about 42.94 months)

Outcome Measure

Overall Survival